Domino Knoevenagel-cyclization reactions of styrene substrates, containing an N-(ortho-formyl)aryl subunit, were carried out with N-substituted 2-cyanoacetamides to prepare tetrahydro-4H-pyrano[3,4-c]quinolone and hexahydrobenzo[j]phenanthridine derivatives by competing IMHDA and IMSDA cyclization, respectively. The diastereoselective IMHDA step with α,β-unsaturated amide, thioamide, ester and ketone subunits as a heterodiene produced condensed chiral tetrahydropyran or thiopyran derivatives, which in the case of Meldrum's acid were reacted further with amine nucleophiles in a multistep domino sequence. In order to simplify the benzene-condensed tricyclic core of the targets and get access to hexahydro-1H-pyrano[3,4-c]pyridine derivatives, a truncated substrate was reacted with cyclic and acyclic active methylene reagents in diastereoselective Knoevenagel-IMHDA reactions to prepare novel condensed heterocyclic scaffolds. The chemo-, regio- and diastereoselectivity of the cyclization step were investigated and structural elucidation was aided by single crystal X-ray analysis.